title: Early prediction of response to sorafenib in patients with advanced hepatocellular carcinoma: the role of dynamic contrast enhanced ultrasound.
abstract: OBJECTIVE
  Sorafenib has become the standard first-line treatment for patients with advanced HCC and acts by inducing alterations in tumor vascularity. We wanted to evaluate the feasibility of dynamic CEUS (D-CEUS) as a predictor of early tumor response to sorafenib and to correlate functional parameters with clinical efficacy end points.
  
  
  METHODS
  Twenty-eight HCC patients treated with sorafenib 400mg bid were prospectively enrolled. CEUS was performed at baseline (T0) and after 15 (T1) and 30 (T2) days of treatment. Tumor vasculature was assessed in a specific harmonic mode associated with a perfusion and quantification software (Q-Lab, Philips). Variations between T1/T2 and T0 were calculated for five D-CEUS functional parameters (peak intensity, PI; time to PI, TP; area under the curve, AUC; slope of wash in, Pw; mean transit time, MTT) and were compared for responders and non-responders. The correlation between D-CEUS parameters, overall survival (OS), and progression-free survival (PFS) was also assessed. A p value <0.05 was considered statistically significant.
  
  
  RESULTS
  The percentage variation at T1 significantly correlated with response in three D-CEUS parameters (AUC, PI and Pw; p=0.002, <0.001, and 0.003, respectively). A decrease of AUC (p=0.045) and an increased/unchanged value of TP (p=0.029) and MTT (p=0.010) were associated with longer survival. Three D-CEUS parameters (AUC, TP, Pw) were significantly associated with PFS.
  
  
  CONCLUSIONS
  D-CEUS provides a reliable and early measure of efficacy for anti-angiogenic therapies and could be an excellent tool for selecting patients who will benefit from treatment.
authors.affiliation: Dept. of Internal Medicine, Catholic University of Rome, Italy. Electronic address: mariaazocco@hotmail.com.
authors.forename: Maria Assunta
authors.initials: MA
authors.lastname: Zocco
authors.forename: Matteo
authors.initials: M
authors.lastname: Garcovich
authors.forename: Andrea
authors.initials: A
authors.lastname: Lupascu
authors.forename: Enrico
authors.initials: E
authors.lastname: Di Stasio
authors.forename: Davide
authors.initials: D
authors.lastname: Roccarina
authors.forename: Brigida Elenora
authors.initials: BE
authors.lastname: Annicchiarico
authors.forename: Laura
authors.initials: L
authors.lastname: Riccardi
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Ainora
authors.forename: Francesca
authors.initials: F
authors.lastname: Ponziani
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Caracciolo
authors.forename: Gian Lodovico
authors.initials: GL
authors.lastname: Rapaccini
authors.forename: Raffaele
authors.initials: R
authors.lastname: Landolfi
authors.forename: Massimo
authors.initials: M
authors.lastname: Siciliano
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pompili
authors.forename: Antonio
authors.initials: A
authors.lastname: Gasbarrini
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000401:mortality; D018450:Disease Progression; D018572:Disease-Free Survival; D023381:Endpoint Determination; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008099:Liver / Q000000981:diagnostic imaging / Q000473:pathology; D008113:Liver Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012189:Retrospective Studies; D000077157:Sorafenib; D015996:Survival Rate; D016896:Treatment Outcome; D014463:Ultrasonography
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib
keywords: Dynamic contrast enhanced ultrasound; Hepatocellular carcinoma; Sorafenib; Tumour response